The Johns Hopkins University

University System of Maryland

Hui Zhang

Daniel W Chan

Shuang Yang

Xingde Li

Shuwei Li

Shadi Toghi Eshghi

Zhen Zhang

Xiangchun Wang

Yuan Tian

Jing Chen

Yan Li

Danni Li

Lori J Sokoll

The presently disclosed subject matter provides methods using mass spectrometry for direct profiling of N-linked glycans from a biological sample. In addition, the embodiments of the present invention also disclose novel methods, known as targeted analyte detection (TAD), for improving the detection limit of MALDI-MS. These methods take advantage of the carrier effect of the added standard analytes, which occurs due to the generic sigmoidal shape of the calibration curve. The functionality of TAD depends on the relative enhancement of sensitivity over the increase of the standard deviation at the analysis of target analytes with spiking in exogenous concentration. At certain ranges of exogenous concentration, the increment in the sensitivity overcomes the standard deviation, resulting in an improved LOD. Theoretically, exogenous concentrations approximately at 1 LODorig would generate the optimum LOD improvement. TAD is a cost-effective LOD improvement method, which is not limited to a certain group of analytes, or detection methods or instruments. It can be applied to enhance the detection of any analyte with different detection methods, provided that the analyte of interest can be extracted or is available in synthetic form.

Mass spectrometry imaging of glycans from tissue sections and improved analyte detection methods

Highly specific and novel methods for analyzing glycans and proteoglycans are provided. The present invention provides glycan-reactive isobaric Aldehyde-Reactive Tags (iARTs) and the quantification of iARTs-labeled glycans by tandem mass spectrometry. The iARTs have an amine as an active group to react with aldehyde at the reducing end of glycans through reductive amination and demonstrated complete labeling. Due to the isobaric nature of the iARTs, differentially labeled glycans do not differ in mass, and quantitative information is provided by the isotope-encoded reporter ions generated from MS/MS or MSspectra. Quantitative information is thus derived from signal of the reporter ions on same precursor. Uses of the information generated by the inventive methods for diagnosis and treatment are also disclosed.

Isobaric aldehyde-reactive tags for and analysis of glycans using same

The disclosure provides quaternary ammonium containing isobaric tag reagents useful in the analysis of biomolecules and methods of making and using the quaternary ammonium containing isobaric tag reagents. The quaternary ammonium containing isobaric tag reagents are particularly useful for glycan analysis, especially quantitative glycan profiling such as glycan quantitation by tandem mass spectrometry.

Quaternary ammonium containing isobaric tag for quantitative glycan profiling

Highly specific and novel methods for analyzing glycans and proteoglycans are provided. Uses of the information generated by the inventive methods for diagnosis and treatment are also disclosed.

The present invention relates to the field of biomarkers. More specifically, the present invention relates to biomarkers useful in diagnosing aggressive prostate cancer. In one embodiment, a method for identifying patients as having or likely to have aggressive prostate cancer comprises the steps of (a) obtaining a biological sample from the patient; (b) performing an assay on the biological sample to detect fucosylated fucosylated DPP-4, sTIE-2, sVEGFR-1, and FUT8; and (c) identifying the patient as having or likely to have aggressive prostate cancer if there is a statistically significant difference in the levels of fucosylated TIMP-1, fucosylated DPP-4, sTIE-2, sVEGFR-1 and FUT8.

Biomarkers for aggressive prostate cancer

The present invention relates to the field of biomarkers and, more specifically, to biomarkers useful in diagnosing aggressive prostate cancer. In specific embodiments, a method for diagnosing aggressive prostate cancer in a patient comprises (a) measuring the levels of one or more biomarkers in a sample collected from the patient; and (b) comparing the levels of the one or more biomarkers with predefined levels of the same biomarkers that correlate to a patient having aggressive prostate cancer and predefined levels of the same biomarkers that correlate to a patient not having aggressive prostate cancer, wherein a correlation to one of the predefined levels provides the diagnosis. In a specific embodiment, the one or more biomarkers may comprise cathepsin-L (CTSL), periostin, microfibrillar-associated protein 4 (MFAP4), collagen XII, neprilysin, clusterin, neutrophil gelatinase associated lipocalin (NGAL), epithelial cell activating molecule (EpCAM), prostate specific antigen (PSA), membrane metallo-endopeptidase (MME) and asporin (ASPN).

The instant invention provides methods and compositions for the detection of prostate cancer is a subject. In one embodiment, a method of detecting prostate cancer in a subject comprises the steps of (a) detecting the presence of at least one biomarker listed in Table 1 in a serum sample, wherein the presence of the biomarker in the serum sample is indicative of prostate cancer.

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Ellicott City, MD, United States of America

Hui Zhang